Have you ever been sick and irritable about every little thing, even toward those who are trying to help you feel better? Low serotonin levels may be to blame. Low levels of serotonin are associated with complaints such as mood issues/swings, anxiousness, sleep disturbances, or difficulty regulating temperature. Interestingly, serotonin signaling is affected by chronic inflammation. Serotonin levels drop in individuals with chronic inflammation due to the shunting of tryptophan into the “kynurenine pathway” (see Figure 1 below), which can contribute to symptoms associated with low serotonin.

Figure 1. Kynurenine Pathway. Tryptophan can be converted into 5-HTP or kynurenine. Pro-inflammatory cytokines can activate the enzyme indoleamine 2,3-dioxygenase (IDO) and shunt tryptophan away from conversion to 5-HTP into the kynurenine and quinolinic acid pathway.

Dantzer et al. (2008) found that high levels of pro-inflammatory cytokines led to decreased serotonin synthesis by shunting tryptophan into the kynurenine pathway.

Maes et al. (2011) also found that activation of IL-6, IFN-γ, TNF-α, and oxidative stress in the body can lead to activation of IDO, and an increased cortisol (which is also indicative of immune up-regulation) can increase the activity of tryptophan dioxygenase (TDO), both of which shunt tryptophan into the kynurenine and quinolinic acid pathways. This leads to a reduction in endogenous serotonin synthesis.

Low serotonin levels, especially in combination with other signs of immune upregulation (see our previous NeuroImmune Transmitters posts, and watch for additional posts), can be an indicator of immune activation because of the shunting of tryptophan into the kynurenine and quinolinic acid pathways. Be sure to consider possible immune triggers when addressing a low serotonin.

References

Dantzer, R., et al. (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews, 9: 46-57.

Maes, M., et al. (2011). The new serotonin hypothesis of depression: Cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Progress in Neuro-psychopharmacology & Biological Psychiatry, 35(3): 702-21.